Efficacy and safety of mipomersen in treatment of dyslipidemia: a meta-analysis of randomized controlled trials.

Abstract

BACKGROUND:

Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in people at risk for cardiovascular diseases. Mipomersen inhibits apolipoprotein B-100 (apoB) synthesis and causes reduction in LDL-C by reducing apoB.

OBJECTIVE:

We aimed to perform a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia.

METHODS:

We searched PUBMED, CENTRAL, and EMBASE from inception through March 2014 and used random-effects model to compute the effect size.

RESULTS:

We identified 8 randomized controlled trials (n = 462). Mipomersen compared with placebo significantly reduced LDL-C by 32.37% (95% confidence interval, 25.55-39.18; P < .00001), total cholesterol by 24.18% (18.54-29.83; P < .00001), very low-density lipoprotein cholesterol by 21.59% (9.16-34.02; P = .0007), non-high-density lipoprotein cholesterol (HDL-C) by 30.83% (23.92-37.74; P < .00001), and triglycerides by 36.26% (22-50.54; P < .00001). It also significantly reduced apoB, lipoprotein(a), and apolipoprotein A1. However, mipomersen did not significantly change HDL-C levels. In safety analysis, mipomersen compared with placebo increased the risks of injection-site reaction (risk ratio, 2.05; 95% confidence interval, 1.39-3.04; P = .0003), flu-like symptoms (1.63; 1.22-2.17; P = .0008), alanine aminotransferase ≥3X upper limit of normal (4.44; 1.67-11.86; P = .003), and hepatic steatosis (3.85, 1.39-10.67; P = .01). The risks of alanine aminotransferase ≥10X upper limit of normal did not reach statistical significance (1.57; 0.32-7.6, P = .58).

CONCLUSION:

Mipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo.

• Authors: Raju Panta, Khagendra Dahal, Sumit Kunwar
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2015 Mar-Apr Vol. 9 Issue 2 Pg. 217-25 ISSN: 1933-2874 [Print] United States
• PMID: 25911078 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein B-100
• Biomarkers, Pharmacological
• Cholesterol, HDL
• Oligonucleotides
• Receptors, LDL
• Triglycerides
• mipomersen

Topics

• Apolipoprotein B-100 (blood)
• Biomarkers, Pharmacological (blood)
• Cardiovascular Diseases (blood, drug therapy, pathology)
• Cholesterol, HDL (blood)
• Dyslipidemias (blood, drug therapy, pathology)
• Fatty Liver (chemically induced, pathology)
• Humans
• Oligonucleotides (adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic
• Receptors, LDL (blood)
• Triglycerides (blood)